Safety of TKI258 in Advanced/Metastatic Melanoma Subjects

Melanoma Clinical Trial

Official title:

A Phase I/II Dose Escalating Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of TKI258 (CHIR-258) in Patients With Locally Advanced or Metastatic Melanoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00303251
• Other study ID #: CTKI258A2105
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: April 2006

Study information

• Verified date: February 2013
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is an open-label, dose-escalating study to delineate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of TKI258. Pharmacokinetics and pharmacodynamics will be performed on all subjects. The eligible subject population consists of subjects who have been diagnosed with locally advanced or metastatic melanoma that is refractory to standard therapy or for which no curative standard therapy exists.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. primary completion date: September 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Confirmed diagnosis of locally advanced or metastatic melanoma (American Joint Committee on Cancer [AJCC] stage IIIB, IIIC or IV) that is refractory to standard therapy or for which no curative standard therapy exists.

• Measurable disease

• Must be eighteen years of age or older

• Must meet baseline laboratory requirements

• ECOG performance status 0 or 1

• Adults of reproductive potential must agree to use effective contraception or be sterile

Exclusion Criteria:

• Concurrent therapy with any other investigational agent

• Uncontrolled central nervous system metastases

• Impaired cardiac function or clinically significant cardiac disease

• Received

• chemotherapy, targeted therapy or monoclonal antibody therapy =4 weeks

• biological therapy or immunotherapy (therapeutic or diagnostic) =2 weeks

• an investigational agent (therapeutic or diagnostic) =4 weeks prior to starting study drug or has not recovered from side effects of such therapy

• Received any hematopoietic colony-stimulating factor (e.g., G-CSF, GM-CSF) = 2 weeks prior to starting study drug. Erythropoietin is allowed.

• Has undergone major surgery = 2 weeks prior to starting study drug or has not recovered from side effects of such surgery.

• Malabsorption syndrome or uncontrolled gastrointestinal symptoms such as nausea, diarrhea, vomiting

• Pregnant or breast feeding women

• History of another primary malignancy that is currently clinically significant or currently requires active intervention.

• Chronic anticoagulation therapy with full strength aspirin, Coumadin, or heparin.

• History of thromboembolic or cerebrovascular events within the last 12 months.

• History of rectal bleeding, bloody vomit, or spitting up blood within the last 3 months.

• Known diagnosis of HIV infection (HIV testing is not mandatory)

• Use of ketoconazole, erythromycin, carbamazepine, phenobarbital, phenytoin, rifampin, St. John's wort and quinidine is prohibited.

• Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study-drug administration or may interfere with the interpretation of study results and, in the judgment of the investigator, make the patient inappropriate for this study

Related Conditions & MeSH terms

• Melanoma

Intervention

Drug:
• TKI258

Locations

Country	Name	City	State
United States	MD Anderson Cancer	Houston	Texas
United States	James Graham Brown Cancer Center	Louisville	Kentucky
United States	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Expansion: Determine the maximum tolerated dose based on dose limiting toxicity of TKI258		end of dose escalation
Primary	Dose Expansion: Determine the plasma and whole blood pharmacokinetics of orally administered TKI258		PK run-in days 1 & 2, cycle 1 days 1, 8, 15, 16, 28, cycle 2 day 15, cycle 2+ day 28
Primary	Dose Escalation: Assess tumor response according to RECIST as measured by response rate and lack of early progressive disease (<=2 months)		every 8 weeks
Secondary	Assess the safety profile of TKI258 in this patient population		PK run in day 1 & 2, cycle 1 day 8, 15, 28, cycle 2+ day 15 & 28, end of study
Secondary	Assess the effect of TKI258 on biomarkers in the blood		PK run day 1 & 2, cycle 1 day 2, 15, 28, cycle 2+ day 28, end of study
Secondary	Assess biomarker changes in tumor/nevi biopsies and archival tumor tissues where accessible, pre- and post-treatment		baseline, cycle 1 day 15, end of study
Secondary	Assess changes in tumor glucose metabolism/cell viability between pre- and post-treatment using [18F]-FDG-PET		baseline, cycle 1 day 15, cycle 2 day 28
Secondary	Assess anti-angiogenic effects of TKI258 using DCE-MRI pre- and post-treatment		baseline, cycle 1 day 2 and cycle 2 day 28

External Links

•   Results for (Study ID) from the Novartis Clinical Trials website